2D materials with intriguing properties have been widely used in optoelectronics. However, electronic devices suffered from structural damage due to the ultrathin materials and uncontrolled defects ...at interfaces upon metallization, which hindered the development of reliable devices. Here, a damage‐free Au/h‐BN/Au memristor is reported using a clean, water‐assisted metal transfer approach by physically assembling Au electrodes onto the layered h‐BN which minimized the structural damage and undesired interfacial defects. The memristors demonstrate significantly improved performance with the coexistence of nonpolar and threshold switching as well as tunable current levels by controlling the compliance current, compared with devices with evaporated contacts. The devices integrated into an array show suppressed sneak path current and can work as both logic gates and latches to implement logic operations allowing in‐memory computing. Cross‐sectional scanning transmission electron microscopy analysis validates the feasibility of this nondestructive metal integration approach, the crucial role of high‐quality atomically sharp interface in resistive switching, and a direct observation of percolation path. The underlying mechanism of boron vacancies‐assisted transport is further supported experimentally by conductive atomic force microscopy free from process‐induced damage, and theoretically by ab initio simulations.
A damage‐free Au/h‐BN/Au memristor fabricated using a metal transfer approach is demonstrated. Au electrodes are physically assembled onto layered h‐BN with minimized damage and interfacial defects. The Au/h‐BN/Au memristors demonstrate superior performance with the coexistence of nonpolar and threshold switching and can further implement logic functions. Cross‐sectional STEM validates the feasibility of this nondestructive approach, the crucial role of sharp interface, and a direct observation of percolation path.
Instagram is currently the most popular social media app among young people around the world. More than 70% of people between the ages of 12 and 24 are Instagram users. The research framework of this ...study was constructed based on smartphone addiction and the uses and gratifications theory. We used 27 question items divided into five factors, namely social interaction, documentation, diversion, self-promotion, and creativity, to investigate the motives for Instagram use and topics of interest among university students in Taiwan. A total of 307 valid questionnaires were obtained. The results revealed that on the whole, the motives for Instagram use were mostly to look at posts, particularly involving social interaction and diversion motives. The level of agreement expressed toward motives for creating posts was lower. Gender, professional training background, and level of addiction to Instagram all exert influence on motives for Instagram use. Over half of the students majoring in design followed artisans and celebrities (including designers), and female students noticed ads on Instagram more than male students did.
Autophagy, a conserved cellular degradation and recycling process, can be enhanced by nutrient depletion, oxidative stress or other harmful conditions to maintain cell survival. ...6-Hydroxydopamine/ascorbic acid (6-OHDA/AA) is commonly used to induce experimental Parkinson's disease (PD) lesions by causing oxidative damage to dopaminergic neurons. Activation of autophagy has been observed in the 6-OHDA-induced PD models. However, the mechanism and exact role of autophagy activation in 6-OHDA PD model remain inconclusive. In this study, we report that autophagy was triggered via mucolipin 1/calcium/calcineurin/TFEB (transcription factor EB) pathway upon oxidative stress induced by 6-OHDA/AA. Interestingly, overexpression of TFEB alleviated 6-OHDA/AA toxicity. Moreover, autophagy enhancers, Torin1 (an mTOR-dependent TFEB/autophagy enhancer) and curcumin analog C1 (a TFEB-dependent and mTOR-independent autophagy enhancer), significantly rescued 6-OHDA/AA-induced cell death in SH-SY5Y cells, iPSC-derived DA neurons and mice nigral DA neurons. The behavioral abnormality of 6-OHDA/AA-treated mice can also be rescued by Torin 1 or C1 administration. The protective effects of Torin 1 and C1 can be blocked by autophagy inhibitors like chloroquine (CQ) or by knocking down autophagy-related genes TFEB and ATG5. Taken together, this study supports that TFEB-mediated autophagy is a survival mechanism during oxidative stress and pharmacological enhancement of this process is a neuroprotective strategy against oxidative stress-associated PD lesions.
Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases, and there are controversial reports regarding the diversity of the associated vaginal microbiota. We ...determined the vaginal microbial community in patients with VVC, bacterial vaginosis (BV), and mixed infection of VVC and BV using Illumina sequencing of 16S rRNA tags. Our results revealed for the first time the highly variable patterns of the vaginal microbiome from VVC patients. In general, the alpha-diversity results of species richness and evenness showed the following order: normal control < VVC only < mixed BV and VVC infection < BV only. The beta-diversity comparison of community structures also showed an intermediate composition of VVC between the control and BV samples. A detailed comparison showed that, although the control and BV communities had typical patterns, the vaginal microbiota of VVC is complex. The mixed BV and VVC infection group showed a unique pattern, with a relatively higher abundance of Lactobacillus than the BV group and higher abundance of Prevotella, Gardnerella, and Atopobium than the normal control. In contrast, the VVC-only group could not be described by any single profile, ranging from a community structure similar to the normal control (predominated with Lactobacillus) to BV-like community structures (abundant with Gardnerella and Atopobium). Treatment of VVC resulted in inconsistent changes of the vaginal microbiota, with four BV/VVC samples recovering to a higher Lactobacillus level, whereas many VVC-only patients did not. These results will be useful for future studies on the role of vaginal microbiota in VVC and related infectious diseases.
Background
Malignant pleural effusion (MPE)-macrophage (Mφ) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1–M2 transition. The M1/M2 features of MPE-Mφ and their ...significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear.
Methods
Total 147 stage-IV lung adenocarcinoma patients undergoing MPE drainage were enrolled for profiling and validation of their M1/M2 spectrum. In addition, the MPE-Mφ signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-Mφ on anti-cancer activity was examined.
Results
We found that MPE-Mφ expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-Mφ displayed diverse PD-L1 expression patterns, while the low PD-L1 expression group was correlated with higher levels of IL-10. Among these markers, we identified a novel two-gene MPE-Mφ signature, IL-1β and TGF-β1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-Mφ patient cohort (
N
= 60,
p
= 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (
N
= 478,
p
< 0.0001). Significantly, β-glucan worked synergistically with IFN-γ to reverse the risk signature by repolarizing the MPE-Mφ toward the M1 pattern, enhancing anti-cancer activity.
Conclusions
We identified MPE-Mφ on the M1/M2 spectrum and plasticity and described a two-gene M1/M2 signature that could predict the outcome of late-stage lung cancer patients. In addition, we found that “re-education” of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.
Cancer cells typically exhibit aberrant DNA methylation patterns that can drive malignant transformation. Whether cancer cells are dependent on these abnormal epigenetic modifications remains ...elusive. We used experimental and bioinformatic approaches to unveil genomic regions that require DNA methylation for survival of cancer cells. First, we surveyed the residual DNA methylation profiles in cancer cells with highly impaired DNA methyltransferases. Then, we clustered these profiles according to their DNA methylation status in primary normal and tumor tissues. Finally, we used gene expression meta-analysis to identify regions that are dependent on DNA methylation-mediated gene silencing. We further showed experimentally that these genes must be silenced by DNA methylation for cancer cell survival, suggesting these are key epigenetic events associated with tumorigenesis.
► An approach to discriminate between “driver” and “passenger” epigenetic events ► Cancer cells become dependent on DNA methylation of a few key target genes ► Somatic cells depend on DNA methylation to silence some germline-specific genes ► Cells in culture rely on aberrant DNA methylation for survival
The type 2 transmembrane serine protease matriptase is involved in many pathophysiological processes probably via its enzymatic activity, which depends on the dynamic relationship between zymogen ...activation and protease inhibition. Matriptase shedding can prolong the life of enzymatically active matriptase and increase accessibility to substrates. We show here that matriptase shedding occurs via a de novo proteolytic cleavage at sites located between the SEA domain and the CUB domain. Point or combined mutations at the four positively charged amino acid residues in the region following the SEA domain allowed Arg-186 to be identified as the primary cleavage site responsible for matriptase shedding. Kinetic studies further demonstrate that matriptase shedding is temporally coupled with matriptase zymogen activation. The onset of matriptase shedding lags one minute behind matriptase zymogen activation. Studies with active site triad Ser-805 point mutated matriptase, which no longer undergoes zymogen activation or shedding, further suggests that matriptase shedding depends on matriptase zymogen activation, and that matriptase proteolytic activity may be involved in its own shedding. Our studies uncover an autonomous mechanism coupling matriptase zymogen activation, proteolytic activity, and shedding such that a proportion of newly generated active matriptase escapes HAI-1-mediated rapid inhibition by shedding into the extracellular milieu.
Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand.
We identified circulating, ...cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium. A time-dependent decrease in aortic tissue and serum miR-125b levels was also found in both ex vivo and in vivo renal failure models. We examined the levels of circulating, cell-free miR-125b in sera from patients with end-stage renal diseases (n=88) and found an inverse association between the severity of VC and the circulating miR-125b level, irrespective of age or mineral-related hormones (odds ratio, 0.71;
=0.03). Furthermore, serum miR-125b levels on enrollment can predict VC progression years later (for high versus low, odds ratio, 0.14;
<0.01; for the highest versus lowest tertile and middle versus lowest tertile, odds ratio, 0.55 and 0.13;
=0.3 and <0.01, respectively). The uremic VC prediction efficacy using circulating miR-125b levels was also observed in an independent cohort (n=135).
The results suggest that serum miR-125b levels are associated with VC severity and serve as a novel predictive marker for the risk of uremia-associated calcification progression.
In addition to the existing measure of onboard quarantine inspection, including fever screening of arriving passengers, suspected cases screening through history of travelling, occupation, contact ...and cluster (TOCC) inquiring, and health assessments conducting, all health care facilities should reinforce reporting severe cases of pneumonia among people who arrive in Taiwan from Wuhan. ...efforts included reporting criteria of all pneumonia cases, testing and quarantine procedures, preparation of pharmaceutical and medical supplies, capacity ensuring of isolation wards, and public health education (mask wearing, temperature checking, hand washing, avoiding eyes, nose, and mouth touching, environmental disinfection, etc.). In light of the ongoing outbreak, CECC has introduced guidelines for high-risk individuals regarding 1) self-health management (reported cases who have tested negative and met criteria for being released from isolation, or people under “COVID-19 Community-based Surveillance), 2) 14-day home quarantine (with travel history), and 3) 14-day home isolation (who had contact with confirmed cases), and provided quarantine sites with free meals and a US$30 compensation per day during the 14-day period. People who meet the epidemiological criteria within 14 days: 1) History of traveling or living abroad, or contact with symptomatic (fever or other respiratory tract infection symptoms) individuals returning from abroad; 2) History of close contact with symptomatic suspected or confirmed case(s); 3) History of cluster related to confirmed cases are required to report to the CDC and placed for laboratory diagnosis.
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